Bone remodeling is characterized by the continuing processes of osteoblast-mediated
bone formation and osteoclast-mediated bone resorption. Bone metabolism is tightly
regulated at the local level by networks of hormones, cytokines, and other factors. In
pathological conditions of bone remodeling, including osteoporosis and periodontal
diseases, inflammatory cytokines and local mediators are responsible for enhancement of
osteoclast resorption and inhibition of repair at the sites of bone resorption.
TNF-α is a pleiotropic hormone with actions on the differentiation, growth, and
functional activities of normal and malignant cells from numerous tissues, TNF-α has
been proposed as a local mediator of the control of bone turnover in situations of
chronic inflammation, and it has been assumed that the local source of TNF-α is the
monocyte in the adjacent bone marrow or the local circulation. TNF-α is a potent
inducer of bone resorption. TNF-α is known to induce the activation of apoptotic
signaling pathway, which leads to the apoptosis of bone cells.
We demonstrated that treatment of murine osteoblastic MC3T3E1 cells with TNF-α
decreases proliferation as well as alkaline phosphatase (ALP) activity in a dose depenent
manner. In addition, TNF-α increases osteoclast-like cell formation in 1α, 25(OH)2D3
or PGE2-treated bone marrow cell culture. When cells were cultured in TNF-α free α
-MEM, this inhibitory effect of ALP activity was reversible up to 10 ng/ml TNF-α, in
contrast, at the 20 ng/ml TNF-α irreversible. In this concentration, TNF-α may induce
apoptosis in MC3T3E1 cells. In this study, TNF-α induces apoptosis resulting in
chromosomal DNA fragmentation, preceded by JNK/SAPKs and caspase-3 activation.
Our present results show that JNK/SAPKs and caspase-3 are activated by TNF-α,
suggesting that the JNK/SAPKs and caspase-3 participate in the bone resorption,
associated with apoptosis.
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